Objective

Methods

A review was conducted using search terms including HPV and penile cancer. Studies using polymerase chain reaction (PCR) assays for HPV DNA detection in invasive penile carcinoma were included.

Results

A total of 1,266 squamous cell carcinoma (SCC) cases contributed data from 30 studies. The number of SCC was similar in Europe (28.2%), North America (27.6%), South America (23.9%) and Asia (20.4%). All SCC were histologically confirmed with biopsies for DNA detection. Most commonly used PCR primers were type-specific (35.2%), and combination PCR (18.2%). HPV prevalence was 47.9%, ranging from 22.4% in verrucous SCC to 66.3% for the basaloid/warty subtypes. HPV16 (30.8%), HPV6 (6.7%) and HPV18 (6.6%) were the most prevalent types. HPV16 and/or HPV 18 prevalence was 36.7%.

Conclusions

HPV DNA was detected in half of SCC, with HPV16 being the most common type. If proven efficacious in men, prophylactic vaccines targeting carcinogenic types HPV16 and 18 could potentially reduce approximately one-third of incident SCC.

Keywords

Notes

Acknowledgments

The authors gratefully acknowledge the funding for this research recieved from the Center of Excellence in Parmacoepidemiology, The University of North Carolina, USA, and GlaxoSmithKline (GSK), U.K. Jennifer Smith received research grants and other financial supports from GSK and Merck Corporation, in addition, provided financial support to Johns Hopkins University, USA, with the latter’s faculty member Robert Kurman also officiating as the principal investigator on the Merck Pathology Panel. Jeanne Pimenta is a full time employee of GSK. The authors also thank Mark Stoler and Edyta Pirog for their helpful comments on this research article, and Yuli Chang for her help with double data abstraction. Financial support: The University of North Carolina Center of Excellence in Pharmacoepidemiology and GlaxoSmithKline provided funding for this research.

Appendix A

Type Specific Human Papillomavirus (HPV) Prevalence among men with invasive penile cancer by study and region

First author

Reference

Country

HPV DNA source

PCR primers used

N cases

HPV prevalence (% of all cases tested)

any

16

18

45

68

52

31

35

51

33

56

58

59

39

6

5

22

74

53

11

70

34

54

28

8

Asia

Chan KW

J Clin Path, 1994

China (n = 1 from Vietnam)

Fixed biopsies

TS-PCR

41

14.6

9.8

9.8

Qiang D

Chin J Surg, 1996

China

Fixed biopsies

TS-PCR

28

60.6

50.0

10.7

Iwasawa A

J Urol, 1993

Japan

Fixed biopsies

TS-PCR

111

63.1

61.3

1.8

0.0

Suzuki H

Jpn J Clin Oncol, 1994

Japan

Fresh + Fixed biopsies

L1 + E6 PCR

13

53.8

30.8

0.0

0.0

7.7

15.4

0.0

0.0

0.0

Senba M

J Med Virol, 2006

Thailand

Fixed biopsies

SPF10

65

81.5

1.5

55.4

0.0

0.0

0.0

0.0

0.0

0.0

0.0

0.0

0.0

0.0

0.0

43.1

1.5

1.5

0.0

1.5

0.0

3.1

1.5

Europe

Liegl B

Am J Surg Pathol, 2004

Austria

Fixed biopsies

TS-PCR

5

100.0

100.0

0.0

Humbey O

E J Cancer, 2003

France

Fixed biopsies

MY09/11 + FAP59/64 +TS-PCR

36

66.7

25.0

0.0

0.0

0.0

0.0

0.0

0.0

0.0

0.0

0.0

0.0

5.6

0.0

0.0

Perceau G

Br J Dermatol, 2003

France

Fixed biopsies

GP5/6 + TS-PCR

17

35.3

17.6

0.0

0.0

0.0

Protzel C

Histol Histopathol, 2007

Germany

Fixed biopsies

TS-PCR

19

36.8

26.3

0.0

Dianzani C

New Microbiol, 2004

Italy

Fixed biopsies

MY09/11 + TS-PCR

2

100.0

0.0

0.0

0.0

0.0

0.0

100.0

Gentile V

Int J Immunopathol Pharmacol, 2006

Italy

Fixed biopsies

MY09/11 + GP5+/6+

11

72.7

45.5

18.2

0.0

0.0

0.0

0.0

0.0

0.0

0.0

0.0

0.0

0.0

0.0

0.0

9.1

0.0

0.0

0.0

0.0

0.0

Nasca MR

J Am Acad Dermatol, 1999

Italy

Fixed biopsies

TS-PCR

4

75.0

75.0

Tornesello ML

Int J Cancer, 2008

Italy

Fixed biopsies

MY09/11 + GP5+/6+ + TS-PCR

41

46.3

43.9

2.4

0.0

0.0

0.0

0.0

0.0

0.0

0.0

0.0

0.0

0.0

0.0

0.0

0.0

0.0

0.0

Lont AP

Int J Cancer, 2006

Netherlands

Fixed biopsies

GP5+/6+

171

29.2

22.2

1.8

1.8

0.0

0.0

0.0

0.0

0.0

1.2

0.6

0.6

0.6

0.0

Pascual A

Histol Histopathol, 2007

Spain

Fixed biopsies

MY09/11 + GP5+/6+

49

77.6

65.3

8.2

0.0

0.0

0.0

0.0

0.0

0.0

0.0

0.0

0.0

0.0

0.0

0.0

0.0

0.0

0.0

0.0

0.0

0.0

Poblet E

Am J Surg Pathol, 1999

Spain

Fixed biopsies

TS-PCR

2

100.0

50.0

0.0

North America

Salazar EL

Arch Androl, 2005

Mexico

Fixed biopsies

TS-PCR

54

64.8

64.8

Cupp MR

J Urol, 1995

United States

Fixed biopsies

MY09/11 + TS-PCR

45

51.1

37.8

4.4

Daling JRa

Int J Cancer, 2005

United States

Fixed biopsies

MY09/11

43

69.8

58.1

2.3

2.3

4.7

0.0

2.3

4.7

2.3

0.0

Gregoire Lb

J Natl Cancer Inst, 1995

United States

Fixed biopsies

TS-PCR

56

25.0

Kiyabu MT

Am J Surg Pathol, 1989

United States

Fixed biopsies

TS-PCR

5

40.0

40.0

0.0

Rubin MA

Am J Pathol, 2001

United States

Fixed biopsies

SPF10

87

45.0

29.9

1.1

1.1

3.4

4.6

1.1

1.1

1.1

0.0

0.0

0.0

0.0

0.0

1.1

1.1

0.0

0.0

1.1

0.0

1.1

Sarkar FH

J Urol, 1992

United States

Fixed biopsies

TS-PCR

12

75.0

75.0

0.0

0.0

0.0

Varma VA

Hum Pathol, 1991

United States

Fixed biopsies

TS-PCR

18

50.0

50.0

0.0

0.0

Wiener JS

Int J Cancer, 1992

United States

Fixed biopsies

TS-PCR

29

31.0

27.6

3.4

South America

Picconi MA

J Med Virol, 2000

Argentina

Fixed biopsies

GP5/6

34

70.6

23.5

32.4

0.0

0.0

5.9

0.0

Bezerra AL

Cancer, 2001

Brazil

Fixed biopsies

GP5/6

82

30.5

15.9

4.9

1.2

0.0

0.0

0.0

0.0

0.0

Levi JE

In J Cancer, 1998

Brazil

fresh biopsies

MY09/11

50

56.0

32.0

6.0

0.0

Nascimento PS

Prog Urol, 2004

Brazil

fresh biopsies

MY09/11 + TS-PCR

16

37.5

6.3

0.0

6.3

12.5

6.3

Gregoire Lb

J Nat Cancer Inst, 1995

Paraguay

Fixed biopsies

TS-PCR

61

19.7

Rubin MA

Am J Pathol, 2001

Paraguay

Fixed biopsies

SPF10

54

37.0

18.5

0.0

5.6

0.0

0.0

0.0

3.7

1.9

0.0

0.0

0.0

0.0

0.0

5.6

0.0

1.9

0.0

1.9

0.0

0.0

Dorfman S

Trop Doct, 2006

Venezuela

Fixed biopsies

MY09/11

5

100.0

80.0

20.0

60.0

a Population-based study

b Combined prevalence data for Paraguay and the United States are presented in Fig. 1